A Comparison of Sertraline-reboxetine Combination Therapy Versus Sertraline or Reboxetine Monotherapy in the Treatment of Major Depression.

Sertraline/[S,S]-Reboxetine Combination Versus Sertraline And [S,S]-Reboxetine Monotherapy In Major Depressive Disorder (MDD) In A Double-Blind, Placebo-Controlled, Eight Week Study.

This study was designed to determine if the novel combination of the SSRI, sertraline, and the NRI reboxetine will increase antidepressant efficacy without sacrificing the favorable safety profile of SSRIs.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: sertraline/[S,S]-reboxetine; Drug: sertraline/[S,S]-reboxetine; Drug: sertraline/[S,S]-reboxetine; Drug: sertraline/[S,S]-reboxetine; Drug: sertraline; Drug: sertraline; Drug: Placebo; Drug: [S,S]-reboxetine monotherapy

• Study Type: Interventional
• Enrollment (Actual): 510
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Pärnu, Estonia, 80012
    • Pfizer Investigational Site
  • Tallinn, Estonia, 10614
    • Pfizer Investigational Site
  • Tartu, Estonia, 51008
    • Pfizer Investigational Site
  • Viljandi Mk.
    • Viljandi, Viljandi Mk., Estonia, 71024
      • Pfizer Investigational Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Pfizer Investigational Site
  • Moscow, Russian Federation
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 115522
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 107076
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 127473
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 119034
    • Pfizer Investigational Site
  • Rostov On Don, Russian Federation, 344010
    • Pfizer Investigational Site
  • Smolensk, Russian Federation, 214019
    • Pfizer Investigational Site
  • St Petersburg, Russian Federation, 190121
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 192019
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 193167
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 194214
    • Pfizer Investigational Site
  • Tomsk, Russian Federation, 634014
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must fulfill the criteria for MDD without psychotic features as defined by DSMIV, based on clinical assessment and confirmed by Structural Clinical Interview for DSM-IV Axis I Disorder-Clinical Version (SCID-I) plus the MDD Specifiers included in the Research Version of SCID-I.
• HAM-D (17-item) ≥ 22 at Screening (Visit 1) and > 20 at Baseline (Visit 2).
• Minimum CGI-S ≥ 4 at Screening (Visit 1) and at Baseline (Visit 2).

Exclusion Criteria:

• Known failure to satisfactory respond after adequate dose and duration (12 weeks) of treatment with clomipramine and one SSRI, or with two or more SSRIs.
• Subjects with > 20% HAM-D (17-item) improvement (decrease) from Screening (Visit 1) at Baseline (Visit 2).
• Subjects with uncorrected hypothyroidism or hyperthyroidism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Tablets, orally once per day for 8 weeks
Experimental: Sertraline/[S,S]-Reboxetine-satellite150/4	Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/4mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/6mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine orally for 3 days, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks
Experimental: Sertraline/[S,S]-Reboxetine-satellite150/6	Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/4mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/6mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine orally for 3 days, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks
Active Comparator: sertraline-satellite	Drug: sertraline; Tablets, 50 mg/day orally for 3 days, followed by 100 mg/day orally for 4 and one half weeks, followed by 150 mg/day orally for 3 weeks.; Drug: sertraline; Tablets, 50 mg/day orally for 3 days, followed by 100 mg/day orally for 4 and one half weeks, followed by 150 mg/day orally for 3 weeks
Active Comparator: sertraline-main	Drug: sertraline; Tablets, 50 mg/day orally for 3 days, followed by 100 mg/day orally for 4 and one half weeks, followed by 150 mg/day orally for 3 weeks.; Drug: sertraline; Tablets, 50 mg/day orally for 3 days, followed by 100 mg/day orally for 4 and one half weeks, followed by 150 mg/day orally for 3 weeks
Experimental: Sertraline/[S,S]-Reboxetine-satellite150/2	Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/4mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/6mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine orally for 3 days, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks
Experimental: Sertraline/[S,S]-Reboxetine-main	Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/4mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/4mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/6mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine for 3 days orally, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks.; Drug: sertraline/[S,S]-reboxetine; Tablets, 50mg sertraline/2mg [S,S]-reboxetine orally for 3 days, followed by 100mg sertraline/2mg [S,S]-reboxetine for 4 and one half weeks, followed by 150mg sertraline/2mg [S,S]-reboxetine for 5 and one half weeks
Active Comparator: [S,S]-reboxetine-main	Drug: [S,S]-reboxetine monotherapy; Tablets, 2 mg/day orally for 3 days, followed by 4 mg/day orally for 4 and one half weeks, followed by 6mg/day for 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change from Baseline up to Week 8 (Visit 9) in the Montgomery-Asberg Depression Rating Scale (MADRS) total score as measured by a mixed concentration, suicidal ideation and restlessness.	visits 1-9

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in HAM-D (17-item) total score	Weeks 1, 2, 3, 5, 6, and 8
Change from Baseline in the Hamilton Anxiety Rating Scale (HAM-A) and Apathy Evaluation Scale (AES)	Weeks 5 and 8
The frequency and severity of treatment-emergent adverse events, ECG changes, laboratory and vital signs changes by treatment group using descriptive statistics.	Weeks 1, 2, 3, 5, 6, and 8
Change from Baseline in MADRS total score	Weeks 1, 2, 3, 5, 6, and 8

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Study Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: March 7, 2008
• First Submitted That Met QC Criteria: March 7, 2008
• First Posted (Estimate): March 14, 2008

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Adrenergic Uptake Inhibitors; Sertraline; Reboxetine
• Other Study ID Numbers: A0501075